Specific Remodeling of Splenic Architecture by Cytomegalovirus

PLoS Pathogens

Carl De Trez¹  Carl F Ware¹  Chris A Benedict¹  Ginelle Patterson¹  Kirsten Schneider¹  Sukwon Ha¹ 

[1] Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California, United States of America

关键词: Spleen;    T cells;    Stromal cells;    Chemokines;    Macrophages;    Gene expression;    Lymphoid tissue;    B cells;   

DOI  :  10.1371/journal.ppat.0020016

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Efficient immune defenses are facilitated by the organized microarchitecture of lymphoid organs, and this organization is regulated by the compartmentalized expression of lymphoid tissue chemokines. Mouse cytomegalovirus (MCMV) infection induces significant remodeling of splenic microarchitecture, including loss of marginal zone macrophage populations and dissolution of T and B cell compartmentalization. MCMV preferentially infected the splenic stroma, targeting endothelial cells (EC) as revealed using MCMV-expressing green fluorescent protein. MCMV infection caused a specific, but transient transcriptional suppression of secondary lymphoid chemokine (CCL21). The loss of CCL21 was associated with the failure of T lymphocytes to locate within the T cell zone, although trafficking to the spleen was unaltered. Expression of CCL21 in lymphotoxin (LT)-α–deficient mice is dramatically reduced, however MCMV infection further reduced CCL21 levels, suggesting that viral modulation of CCL21 was independent of LTα signaling. Activation of LTβ-receptor signaling with an agonistic antibody partially restored CCL21 mRNA expression and redirected transferred T cells to the splenic T cell zone in MCMV-infected mice. These results indicate that virus-induced alterations in lymphoid tissues can occur through an LT-independent modulation of chemokine transcription, and targeting of the LT cytokine system can counteract lymphoid tissue remodeling by MCMV.

【 授权许可】

CC BY